Creatine: A Brief History.

The Origin of Creatine.

Creatine was first discovered in 1832 by French chemist Michel Eugène Chevreul.¹ Appearing as a clear, pearl-shining crystal derived from beef broth. The molecule remained a mystery until 1847, when German chemist Justus von Liebig linked creatine to muscle, noting, significantly, that the amount of creatine increased in animals with higher muscle mass.² This discovery inspired intense scientific interest, as well as commercial opportunity. Liebig went on to produce Liebig’s Meat Extract, made from South American beef trimmings and marketed across Europe as nourishment for soldiers and the fatigued.³ At the time, creatine-rich food, such as fish, was also seen as a tool to “nourish the nerves” and was often used by scholars and philosophers with high mental demands. Liebig’s Meat Extract quickly became a sensation, praised in newspapers and stocked in apothecaries and grocers’ shops across the continent.⁴ With roughly 5% creatine content, Liebig’s extract may be considered the first crude creatine supplement.⁵

The 1900s saw the purification of creatine and its first use in human studies, linking 10-gram supplementation of the molecule with weight gain – an early hint of creatine’s effect on tissue hydration and storage.⁶ Its importance in the neuro-muscular system was later discovered in 1928, linking creatine's role in rapid, powerful muscular contractions and followed by the breakthrough of creatines role in rapidly replenishing ATP^7,8 – the bodies primary fuel for muscle contraction and energy in the nervous system. It was then discovered that our bodies produce creatine from the amino acids, arginine, glycine and methionine. This established creatine as both a dietary nutrient (from animal meat) and an endogenously produced compound.⁹

The modern era began in 1992, when Harris, Söderlund, and Hultman demonstrated that oral creatine supplementation significantly increases muscle creatine levels.¹⁰ Shortly after, athlete use accelerated, sports scientists examined performance effects,¹¹ and neuroscience research examined creatine as a brain-energy support molecule.¹²

Creatine's Athletic Debut.

Creatine entered mainstream attention during the 1992 Barcelona Olympics. Reports surfaced that several British athletes, including sprinter Linford Christie, had used it legally as part of their training programs.¹³ At the time, sports authorities did not ban creatine, and the idea of a dietary compound improving performance captured worldwide interest.

The supplement rapidly gained popularity among strength athletes, sprinters, and later among athletes in team sports. Unlike many supplements of that era, creatine's benefits were consistently supported by controlled trials. With research consistently demonstration creatine supplementations link with increased phosphocreatine stores, enhanced short-burst power, and greater training volume.^10,14,15

Creatine monohydrate remains the most trusted form today, backed by decades of studies showing improvements in power output, lean mass gain, and exercise performance.¹⁶ Despite numerous modern formulations, monohydrate remains the benchmark for quality, safety, and results.

Creatine for Cognitive Health.

While creatine is most widely known for its role in athletic performance, interest in its effects on the brain has grown over the past two decades. Early studies in the 2000s suggested that creatine could support cognition under stress by helping maintain ATP levels in brain cells.¹² The brain uses large amounts of energy to support memory, reaction speed, and executive function, and creatine plays a central role in buffering cellular energy demands.

Research has found that creatine may help preserve performance during sleep deprivation, mental fatigue, and hypoxia. It may also support mood, with preliminary studies exploring its role as an add-on therapy in depression.^17-19 Pilot studies have examined creatine in concussion recovery and traumatic brain injury, suggesting possible neuroprotective effects.²⁰ Vegetarians and vegans, who generally have lower baseline creatine levels due to reduced dietary intake, appear to benefit cognitively from supplementation.²¹

Although the field is young, creatine is becoming an essential compound in discussions about brain metabolism, resilience, and healthy ageing. Scientific attention has shifted from viewing creatine as only a sports supplement to recognising it as a molecule with physiological relevance across physical, metabolic, and cognitive health.

References.

1. Chevreul, M. Sur la composition chimique du bouillon de viands. J Pharm Sci Access 21, 231-242 (1835).
2. Liebig, J. Über die Bestandtheile der Flüssigkeiten des Fleisches. Annalen der Chemie und Pharmacie 1847, 281-369 (1847).
3. Gratzer, W. Terrors of the Table: The Curious History of Nutrition.  (Oxford University Press, 2005).
4. Lankester, E. On The Extract of Meat. Nature 2, 62-64 (1870). https://doi.org:10.1038/002062a0
5. Wood, T. & Bender, A. E. Analysis of tissue constituents; commercial ox-muscle extract. Biochem J 67, 366-373 (1957). https://doi.org:10.1042/bj0670366
6. Chanutin, A. & Guy, L. P. THE FATE OF CREATINE WHEN ADMINISTERED TO MAN. Journal of Biological Chemistry 67, 29-41 (1926). https://doi.org:https://doi.org/10.1016/S0021-9258(18)84727-5
7. Eggleton, P. & Eggleton, G. P. The Inorganic Phosphate and a Labile Form of Organic Phosphate in the Gastrocnemius of the Frog. Biochem J 21, 190-195 (1927). https://doi.org:10.1042/bj0210190
8. Fiske, C. H. & Subbarow, Y. The Nature of the "Inorganic Phosphate" in Voluntary Muscle. Science 65, 401-403 (1927). https://doi.org:doi:10.1126/science.65.1686.401
9. Bloch, K. & Schoenheimer, R. THE BIOLOGICAL FORMATION OF CREATINE. The Journal of biological chemistry 133, 633-634 (1940). https://doi.org:10.1016/S0021-9258(18)73347-4
10. Harris, R. C., Söderlund, K. & Hultman, E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 83, 367-374 (1992). https://doi.org:10.1042/cs0830367
11. Greenhaff, P. L. Creatine supplementation: recent developments. Br J Sports Med 30, 276-277 (1996). https://doi.org:10.1136/bjsm.30.4.276
12. Andres, R. H., Ducray, A. D., Schlattner, U., Wallimann, T. & Widmer, H. R. Functions and effects of creatine in the central nervous system. Brain research bulletin 76, 329-343 (2008).
13. Anderson, O. Creatine propels British athletes to Olympic gold medals: Is creatine the one true ergogenic aid. Running Research News 9, 1-5 (1993).
14. Kreider, R. B. et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition 14, 18 (2017). https://doi.org:10.1186/s12970-017-0173-z
15. Branch, J. D. Effect of creatine supplementation on body composition and performance: a meta-analysis. International journal of sport nutrition and exercise metabolism 13, 198-226 (2003).
16. Buford, T. W. et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr 4, 6 (2007). https://doi.org:10.1186/1550-2783-4-6
17. Cuijpers, P. et al. Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients. World Psychiatry 22, 105-115 (2023). https://doi.org:https://doi.org/10.1002/wps.21069
18. Lyoo, I. K. et al. A Randomized, Double-Blind Placebo-Controlled Trial of Oral Creatine Monohydrate Augmentation for Enhanced Response to a Selective Serotonin Reuptake Inhibitor in Women With Major Depressive Disorder. American Journal of Psychiatry 169, 937-945 (2012). https://doi.org:10.1176/appi.ajp.2012.12010009
19. Gordji-Nejad, A. et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports 14, 4937 (2024). https://doi.org:10.1038/s41598-024-54249-9
20. Forbes, S. C. et al. Effects of Creatine Supplementation on Brain Function and Health. Nutrients 14 (2022). https://doi.org:10.3390/nu14050921
21. Benton, D. & Donohoe, R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. British Journal of Nutrition 105, 1100-1105 (2011).